Structural basis for G.C recognition in the DNA minor groove.
Small molecules that target specific DNA sequences offer a potentially general approach for the regulation of gene expression. Pyrrole-imidazole polyamides represent the only class of synthetic small molecules that can bind predetermined DNA sequences with affinities and specificities comparable to DNA binding proteins. Antiparallel side-by-side pairings of two aromatic amino acids, imidazole (Im) and pyrrole (Py), distinguish G.C from C.G, and both from A.T/T.A base pairs. A high resolution X-ray crystal structure of a four-ring pyrrole-imidazole polyamide specifically bound as a dimer to a six-base pair predetermined DNA site reveals a structural framework of hydrogen bonds and interactions with the walls of the minor groove that underlies the pairing rules for DNA recognition.
Kielkopf
C L
CL
Division of Biology, California Institute of Technology, Pasadena 91125, USA.
Baird
E E
EE
Dervan
P B
PB
Rees
D C
DC
D001482:Base Composition; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry*; D003854:Deoxyribonucleotides / Q000138:chemical synthesis / Q000737:chemistry; D019281:Dimerization; D006860:Hydrogen Bonding; D007093:Imidazoles / Q000737:chemistry; D009690:Nucleic Acid Conformation; D011758:Pyrroles / Q000737:chemistry
D003854:Deoxyribonucleotides; D007093:Imidazoles; D011758:Pyrroles; D004247:DNA